|Publication number||US7824624 B2|
|Application number||US 11/784,130|
|Publication date||Nov 2, 2010|
|Filing date||Apr 5, 2007|
|Priority date||Apr 7, 2006|
|Also published as||EP2012923A1, US20070237685, WO2007120515A1|
|Publication number||11784130, 784130, US 7824624 B2, US 7824624B2, US-B2-7824624, US7824624 B2, US7824624B2|
|Inventors||Richard Bergman, William J. Miller, Mark L. Morrell, Todd M. Roswech, Po Ki Yuen|
|Original Assignee||Corning Incorporated|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (20), Non-Patent Citations (1), Classifications (17), Legal Events (2)|
|External Links: USPTO, USPTO Assignment, Espacenet|
This application claims the benefit of U.S. Provisional Application Ser. No. 60/790,188 filed on Apr. 7, 2006 and entitled “Microplate Flow-Through Assay Device”. The contents of this document are hereby incorporated by reference herein.
The present invention relates to a closed flow-through microplate and a method for using the closed flow-through microplate to perform a flow-through assay to detect biomolecular interactions like material bindings, adsorptions etc. . . that is helpful for example with testing new drugs.
Instrumentation for label-free high throughput screening is commercially available today and is often used for detecting biomolecular interactions while testing new drugs. The typical label-free interrogation system employs microplates with wells which have biosensors incorporated therein that enable the detection of biomolecular interactions like material bindings, adsorptions etc. . . by monitoring changes in the refractive index at or near the sensing surfaces of the biosensors. For example, each biosensor has a sensing surface on which a ligand can be immobilized so that when an analyte which is in a solution located above the sensing surface interacts with the immobilized ligand then there would be a change in the refractive index. The label-free interrogation system interrogates each biosensor and detects this change in the refractive index and as a result is able to detect/monitor the biomolecular interaction between the immobilized ligand and the analyte which is useful while testing new drugs.
The typical microplate includes an open array of wells which are aligned with an array of biosensors that are located on the surface of a substrate which forms the bottoms of the wells. These open-air microplates perform well in most applications but there are some applications which require the use of flow-through assays (kinetic assays of association and dissociation) where a micro-fluidic microplate would be preferable to use instead of the open-air microplate. Unfortunately, the existing micro-fluidic microplates, suffer from a problem of maintaining a closed system so one or more fluids can be transferred from a fluid delivery system into the micro-fluidic microplate where they flow over the biosensors and are then removed from the micro-fluidic microplate without being exposed to the air and/or being spilled on top of the micro-fluidic microplate. In other words, there is often a leakage/sealing problem that occurs at the interface between these micro-fluidic microplates and the fluid delivery system.
To address this sealing/leakage problem, the assignee of the present invention has developed several different closed flow-through microplates which were disclosed and discussed in U.S. patent application Ser. No. 10/155,540 filed May 24, 2002 and entitled “Microcolumn-Based, High-Throughput Microfluidic Device” (the contents of this document are incorporated by reference herein). Although these closed flow-through microplates work well when performing a flow-through assay there is still a desire to improve upon and enhance the existing closed flow-through microplates. This particular need and other needs have been satisfied by the present invention
The present invention provides a closed flow-through microplate which is configured as a microplate 2-plate stack that has an upper plate (well plate) attached to a lower plate (sensor plate). The upper plate has a top surface, a body and a bottom surface. The top surface has located thereon a sealing substance which has one or more fluid delivery/removal sealing interfaces where each fluid delivery/removal sealing interface has one or more inlet ports and one or more outlet ports. The body has one or more fluid delivery/removal channels extending therethrough where each fluid delivery/removal channel has one or more inlet channels and one or more outlet channels which are respectively aligned with the one or more inlet ports and the one or more outlet ports located within the corresponding fluid delivery/removal sealing interface. The lower plate has a top surface which is attached to the bottom surface of the upper plate such that one or more flow chambers are present there between, where each one of the flow chambers is in communication with a corresponding one of the fluid delivery/removal channels extending through the body of the upper plate. In addition, the present invention provides methods for the use and the manufacture of the closed flow-through microplate.
A more complete understanding of the present invention may be had by reference to the following detailed description when taken in conjunction with the accompanying drawings wherein:
The well plate 102 has a top surface 110 on which there is a sealing substance 112 which is divided into 96-fluid delivery/removal sealing interfaces 114 (note: the sealing substance 112 has four distinct sections 112 a, 112 b, 112 c and 112 d). In this example, each of the fluid delivery/removal sealing interfaces 114 has two inlet ports 116 and one outlet port 118. However, each of the fluid delivery/removal sealing interfaces 114 could have any number of inlet ports 116 and any number of outlet ports 118. For example, each fluid delivery/removal sealing interface 114 could have three inlet ports 116 and three outlet ports 118. Or, each fluid delivery/removal sealing interface 114 could have one inlet port 116 and one outlet port 118.
The well plate 102 and sensor plate 104 can be attached to one another by using anyone of several different attachment schemes. For instance, the well plate 102 may have a bottom surface 130 which has ridge(s) 138 extending therefrom which enables the formation of the flow chamber(s) 132 when the well plate 102 is attached to the sensor plate 104 (see
At step 304, the fluid delivery system 200 inserts two fluids through one or more sets of the fluid delivery/removal tips 202 and in particular through their fluid delivery tips 204 such that both fluids flow through the flow chamber(s) 132 within the microplate 100 (note: the two fluids 402 a and 402 b would normally flow perpendicular to the grooves/diffraction gratings 404 associated with the biosensor 136—see
At step 308, an interrogation system (not shown) can interrogate the biosensor(s) 136 to detect any changes in the refractive index at or near their sensing surface(s) while the two fluids are flowing within the flow chamber(s) 132 of the microplate 100 (note: step 308 is performed concurrently with steps 304 and 306). For instance, the interrogation system can be used to perform a label independent kinetic flow through assay to detect biomolecular interactions like material bindings, adsorptions etc. . . that is helpful when testing new drugs. An exemplary interrogation system which could interrogate the microplate 100 has been described in a co-assigned U.S. patent application Ser. No. 11/489,173 (the contents of which are hereby incorporated by reference herein). Plus, a discussion about how the interrogation system can perform intra-cell self referencing to help mitigate the uncertainties due to environmental conditions by having two fluids (one sample solution and one reference solution) flow over a single biosensor is provided in a co-assigned U.S. patent application Ser. No. 10/993,565 (the contents of which are hereby incorporated by reference herein).
At step 504, a second mold is used to injection mold the sealing substance 112 (which forms the fluid delivery/removal sealing interfaces 114) into the depressions 111 located on the top surface 110 of the well plate 102 (see
At step 506, the sensor plate 104 has a top surface 128 that is attached via an adhesive to the bottom surface 130 of the well plate 102 in a manner so as to form the flow chamber(s) 132 (see
Although several embodiments of the present invention have been illustrated in the accompanying Drawings and described in the foregoing Detailed Description, it should be understood that the invention is not limited to the embodiments disclosed, but is capable of numerous rearrangements, modifications and substitutions without departing from the spirit of the invention as set forth and defined by the following claims.
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|U.S. Classification||422/402, 422/501|
|Cooperative Classification||B01L2200/025, B01L2200/028, B01L2300/0887, B01L3/565, B01L3/502715, B01L2300/0636, B01L2300/0864, B01L2200/027, B01L3/502738, B01L3/5025, B01L2300/0829|
|European Classification||B01L3/5025, B01L3/5027E, B01L3/5027B|
|Apr 5, 2007||AS||Assignment|
Owner name: CORNING INCORPORATED, NEW YORK
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BERGMAN, RICHARD;MILLER, WILLIAM J.;MORRELL, MARK L.;ANDOTHERS;REEL/FRAME:019211/0953;SIGNING DATES FROM 20070402 TO 20070405
Owner name: CORNING INCORPORATED, NEW YORK
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BERGMAN, RICHARD;MILLER, WILLIAM J.;MORRELL, MARK L.;ANDOTHERS;SIGNING DATES FROM 20070402 TO 20070405;REEL/FRAME:019211/0953
|May 2, 2014||FPAY||Fee payment|
Year of fee payment: 4